U.S. patent application number 12/593860 was filed with the patent office on 2010-04-22 for method of cleaning micro-flow passages.
This patent application is currently assigned to FUJIFILM CORPORATION. Invention is credited to Luc Bousse, Chen Li, Yoshihiro Seto.
Application Number | 20100095986 12/593860 |
Document ID | / |
Family ID | 39808680 |
Filed Date | 2010-04-22 |
United States Patent
Application |
20100095986 |
Kind Code |
A1 |
Seto; Yoshihiro ; et
al. |
April 22, 2010 |
METHOD OF CLEANING MICRO-FLOW PASSAGES
Abstract
To improve cleansing quality of wall surfaces of micro-flow
channels in a micro-flow channel cleansing method. During cleansing
of wall surfaces of micro-flow channels having at least one
branching channel, by causing cleansing fluid to flow therethrough,
the cleansing fluid is caused to flow through the at least one
branching channel such that there is no residual fluid on the wall
surfaces thereof.
Inventors: |
Seto; Yoshihiro;
(Ashigarakami-gum, JP) ; Bousse; Luc; (Mountain
View, CA) ; Li; Chen; (Mountain View, CA) |
Correspondence
Address: |
SUGHRUE MION, PLLC
2100 PENNSYLVANIA AVENUE, N.W., SUITE 800
WASHINGTON
DC
20037
US
|
Assignee: |
FUJIFILM CORPORATION
TOKYO
JP
|
Family ID: |
39808680 |
Appl. No.: |
12/593860 |
Filed: |
March 28, 2008 |
PCT Filed: |
March 28, 2008 |
PCT NO: |
PCT/US08/58624 |
371 Date: |
September 29, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60920832 |
Mar 30, 2007 |
|
|
|
Current U.S.
Class: |
134/22.12 ;
134/22.11 |
Current CPC
Class: |
B08B 9/0321 20130101;
B08B 9/035 20130101 |
Class at
Publication: |
134/22.12 ;
134/22.11 |
International
Class: |
B08B 9/032 20060101
B08B009/032; B08B 9/035 20060101 B08B009/035 |
Claims
1-5. (canceled)
6. A micro-flow channel cleansing method for cleansing wall
surfaces of micro-flow channels having at least one branching
channel, by causing cleansing fluid to flow therethrough,
characterized by: the cleansing fluid being caused to flow through
the at least one branching channel such that there is no residual
fluid on the wall surfaces thereof.
7. A micro-flow channel cleansing method as defined in claim 6,
characterized by: the flow direction of the cleansing fluid with
respect to the at least one branching channel being changed, by
performing injection and suction of the cleansing fluid into and
out of a single micro-flow channel that communicates with the at
least one branching channel.
8. A micro-flow channel cleansing method as defined in claim 6,
characterized by: the flow direction of the cleansing fluid with
respect to the at least one branching channel being changed, by
performing injection and suction of the cleansing fluid into and
out of micro-flow channels that have the at least one branching
channel therebetween and communicate therewith, at least once.
9. A micro-flow channel cleansing method as defined in claim 7,
characterized by: the flow direction of the cleansing fluid with
respect to the at least one branching channel being changed, by
performing injection and suction of the cleansing fluid into and
out of micro-flow channels that have the at least one branching
channel therebetween and communicate therewith, at least once.
10. A micro-flow channel cleansing method as defined in claim 6,
characterized by: the at least one branching channel branching in a
T-shape.
11. A micro-flow channel cleansing method as defined in claim 7,
characterized by: the at least one branching channel branching in a
T-shape.
12. A micro-flow channel cleansing method as defined in claim 8,
characterized by: the at least one branching channel branching in a
T-shape.
13. A micro-flow channel cleansing method as defined in claim 9,
characterized by: the at least one branching channel branching in a
T-shape.
14. A micro-flow channel cleansing method as defined in claim 6,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
15. A micro-flow channel cleansing method as defined in claim 7,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
16. A micro-flow channel cleansing method as defined in claim 8,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
17. A micro-flow channel cleansing method as defined in claim 9,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
18. A micro-flow channel cleansing method as defined in claim 10,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
19. A micro-flow channel cleansing method as defined in claim 11,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
20. A micro-flow channel cleansing method as defined in claim 12,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
21. A micro-flow channel cleansing method as defined in claim 13,
characterized by: the micro-flow channels being formed in a
microchip to be utilized by a clinical analysis apparatus, and
being for reagents and samples to be introduced thereinto.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority to U.S. Provisional
Application Ser. No. 60/920,832, filed on Mar. 30, 2007.
TECHNICAL FIELD
[0002] The present invention relates to a micro-flow channel
cleansing method. More specifically, the present invention relates
to a micro-flow channel cleansing method for cleansing micro-flow
channels provided with branching channels.
BACKGROUND ART
[0003] Electrophoresis apparatuses and chemical processing
apparatuses that utilize micro-flow channel substrates, in which
extremely fine micro-flow channels (for example, 100 .mu.m wide and
15 .mu.m deep) are formed between stacked glass plates, are known
(Patent Document 1).
[0004] The electrophoresis apparatuses introduce sample liquids
containing reagents, samples, buffer liquid and the like into the
micro-flow channels. The electrophoresis apparatuses apply high
voltage (electrophoretic voltage) to the introduced sample liquids
to cause electrophoresis to occur. Measurement target substances
within the samples, such as proteins and nucleic acids, are
separated by electrophoresis and detected at detection points
within the micro-flow channels.
[0005] The chemical processing apparatuses introduce various
liquids into the micro-flow channels as raw materials, administer
chemical processes, and generate fine particles.
[0006] In the aforementioned apparatuses, micro-flow channel
substrates, in which the micro-flow channels are formed, are
repeatedly utilized for measurement. Accordingly, techniques for
reusing the micro-flow channel substrates are known. In these
techniques, cleansing fluid is caused to flow through the
micro-flow channels to cleanse the micro-flow channels after
detection of the measurement target substances or the generation of
the fine particles is completed.
[Patent Document 1]
[0007] Japanese Unexamined Patent Publication No. 2004-243308
[0008] Micro-flow channels which are formed in elongate glass tubes
are linear channels that extend unidirectionally. However, among
micro-flow channels formed in micro-flow channel substrates, there
are those that have two dimensional structures composed of
branching channels. When cleansing fluid is caused to flow through
these micro-flow channels which are provided with branching
channels, there are cases in which residual fluids remain on the
wall surfaces of the branching channels. In these cases, the
cleansing fluid remains on specific wall surfaces within the
branching channels. That is, foreign substances remain on the
specific wall surfaces, even after cleansing.
[0009] Foreign substances remaining on wall surfaces after
cleansing is a problem which is not limited to cleansing of
micro-flow channels of micro-flow channel substrates which are
utilized by the aforementioned electrophoresis apparatuses and
chemical processing apparatuses. This is a common problem which is
encountered when cleansing micro-flow channels provided with
branching channels.
[0010] The present invention has been developed in view of the
foregoing circumstances. It is an object of the present invention
to provide a cleansing method for micro-flow channels that can
improve the quality of cleansing of micro-flow channels.
DISCLOSURE OF THE INVENTION
[0011] A micro-flow channel cleansing method of the present
invention is a micro-flow channel cleansing method for cleansing
wall surfaces of micro-flow channels having at least one branching
channel, by causing cleansing fluid to flow therethrough,
characterized by:
[0012] the cleansing fluid being caused to flow through the at
least one branching channel such that there is no residual fluid on
the wall surfaces thereof.
[0013] In the micro-flow channel cleansing method of the present
invention, the wall surfaces of the at least one branching channel
may be cleansed, by changing the flow direction of the cleansing
fluid with respect to the at least one branching channel. The
change in the flow direction of the cleansing fluid may be realized
by performing injection and suction of the cleansing fluid into and
out of a single micro-flow channel that communicates with the at
least one branching channel.
[0014] In the micro-flow channel cleansing method of the present
invention, the wall surfaces of the at least one branching channel
may be cleansed, by changing the flow direction of the cleansing
fluid with respect to the at least one branching channel. The
change in the flow direction of the cleansing fluid may be realized
by performing injection and suction of the cleansing fluid into and
out of different micro-flow channels that have the at least one
branching channel therebetween and communicate therewith, at least
once.
[0015] The at least one branching channel may branch in a
T-shape.
[0016] The micro-flow channels may be formed in a microchip to be
utilized by a clinical analysis apparatus, and may be for reagents
and samples to be introduced thereinto.
[0017] Note that the phrase "the cleansing fluid being caused to
flow through the at least one branching channel such that there is
no residual fluid on the wall surfaces thereof" means that the
cleansing fluid is caused to flow through the at least one
branching channel such that the cleansing fluid flows across the
entirety of the wall surfaces thereof.
[0018] According to the micro-flow channel cleansing method of the
present invention, the cleansing fluid is caused to flow through
the at least one branching channel such that there is no residual
fluid on the wall surfaces thereof. Therefore, the quality of
cleansing of micro-flow channels can be improved.
[0019] That is, the cleansing fluid is caused to flow through the
at least one branching channel such that the cleansing fluid flows
across the entirety of the wall surfaces thereof such that no
residual fluid remains on the wall surfaces of the at least one
branching channel. Thereby, sample liquids, the cleansing fluid and
the like are prevented from remaining on specific wall surfaces
that constitute the at least one branching channel. Foreign
substances which are adhered to the wall surfaces of branching
channels can be dissolved in the cleansing fluid, or removed by the
force applied thereon by the cleansing fluid. Accordingly, the
foreign substances are positively removed from the wall surfaces,
and the quality of cleansing of the micro-flow channels can be
improved.
[0020] The flow direction of the cleansing fluid with respect to
the at least one branching channel may be changed, by performing
injection and suction of the cleansing fluid into and out of a
single micro-flow channel that communicates with the at least one
branching channel. In this case, the cleansing fluid can be caused
to flow through all of the wall surfaces of the at least one
branching channel more positively, further improving the quality of
cleansing of the micro-flow channels.
[0021] The flow direction of the cleansing fluid with respect to
the at least one branching channel may be changed, by performing
injection and suction of the cleansing fluid into and out of
different micro-flow channels that have the at least one branching
channel therebetween and communicate therewith, at least once. In
this case, the cleansing fluid can be caused to flow through all of
the wall surfaces of the at least one branching channel more
positively, further improving the quality of cleansing of the
micro-flow channels.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] [FIG. 1] a diagram that illustrates an example of a
microchip having micro-flow channels, to which the micro-flow
channel cleansing method of the present invention is applied; FIG.
1A is a perspective view of the microchip viewed from the top
surface thereof, and FIG. 1B is a perspective view of the microchip
viewed from the bottom surface thereof
[0023] [FIG. 2] a plan view that illustrates an example of
micro-flow channels which are formed in the microchip
[0024] [FIG. 3] a diagram that illustrates a comparative example of
a cleansing method for micro-flow channels
[0025] [FIG. 4] a diagram that illustrates how micro-flow channels
are cleansed by a first embodiment of the micro-flow channel
cleansing method; FIG. 4A illustrates a state in which cleansing
fluid is suctioned into a sub flow channel, and FIG. 4B illustrates
a state in which cleansing fluid is injected into the sub flow
channel
[0026] [FIG. 5] a diagram that illustrates how micro-flow channels
are cleansed by a second embodiment of the micro-flow channel
cleansing method; FIG. 5A illustrates a state in which cleansing
fluid is suctioned through a sub flow channel, and FIG. 5B
illustrates a state in which cleansing fluid is suctioned through a
sub flow channel different from the aforementioned sub flow
channel
[0027] [FIG. 6] a perspective view that illustrates the outer
appearance of a clinical analysis apparatus of the present
invention
[0028] [FIG. 7] a magnified perspective view of a measuring section
of the clinical analysis apparatus of FIG. 6, in a state in which
microchips 100 are provided therein
[0029] [FIG. 8] a schematic view that illustrates a stocking
section and a measuring section as the main parts of the clinical
analysis apparatus
[0030] [FIG. 9] a magnified perspective view that illustrates the
main parts of a chemical cleansing station of the clinical analysis
apparatus
[0031] [FIG. 10] a magnified sectional view that illustrates a
state in which a well is cleansed, and a state in which negative
pressure is applied on a well
[0032] [FIG. 11] magnified perspective views of the manner in which
microchips are exchanged at a attaching/removing station of the
clinical analysis apparatus; FIG. 11A illustrates a state in which
a microchip is standing by at the attaching/removing station, and
FIG. 11B illustrates a state in which a microchip is being
discharged from the attaching/removing station
BEST MODE FOR CARRYING OUT THE INVENTION
[0033] Hereinafter, the micro-flow channel cleansing method of the
present invention will be described in detail. FIG. 1 is a diagram
that illustrates an example of a microchip having micro-flow
channels, to which the micro-flow channel cleansing method of the
present invention is applied. FIG. 1A is a perspective view of the
microchip viewed from the top surface thereof, and FIG. 1B is a
perspective view of the microchip viewed from the bottom surface
thereof. FIG. 2 is a plan view that illustrates an example of
micro-flow channels which are formed in the microchip.
[0034] The microchip 100 illustrated in FIG. 1, to which the
micro-flow channel cleansing method of the present invention is
applied, is utilized by a clinical analysis apparatus (for example,
that which detects liver cancer markers). The microchip 100 is
provided with at least one branching channel that branches a flow
channel.
[0035] The microchip 100 is constituted by: a cover 101 formed by
synthetic resin or the like; and a micro-flow channel substrate 102
formed by a substantially rectangular glass plate (a transparent
plate member), for example, provided at the central portion of a
recess 100b on the bottom surface of the cover 101.
[0036] The micro-flow channel substrate 102 is constituted by two
glass plates (refer to FIG. 10). The two glass plates are laminated
together into a single substrate so as to sandwich micro-flow
channels 110 (also referred to as capillaries; hereinafter, simply
referred to as flow channels 110) therebetween. Both of the glass
plates may be transparent. Alternatively, only one of them, through
which light is transmitted when optical measurement (to be
described later) is performed, may be transparent.
[0037] A plurality of cylindrical protrusions, that is, wells 106,
having inner diameters of 1.2 mm for example, are formed on the top
surface, that is, the main surface 100a of the microchip 100. The
positions of the wells 106 are matched to the flow channels 110
formed in the micro-flow channel substrate 102. Well apertures 107,
which are apertures provided within the wells 106, penetrate
through one of the glass plates to communicate with the flow
channels 110.
[0038] Accordingly, if sample fluids containing reagents and
samples are dripped into the wells 106, the sample fluids are
introduced into the flow channels 110. Note that the micro-flow
channel substrate 102 may be formed by a synthetic resin, instead
of glass.
[0039] Next, the flow channels will be described with reference to
FIG. 2. FIG. 2 is a plan view that illustrates an example of flow
channels 110 which are formed in the micro-flow channel substrate
102. The flow paths 110 are 100 .mu.m wide and 15 .mu.m deep, for
example. The flow channels 110 are formed by a micro processing
technique, such as etching or photolithography. Note that two or
more sets of independent flow channels may be formed in the
microchip 100.
[0040] The flow channels 110 are constituted by: a main flow
channel 110a that extends linearly in the horizontal direction of
FIG. 2, shorter sub flow channels 110b through 110f that branch
from the main flow channel 110a at right angles and extends for
short distances, and a flow channel ef. The aforementioned well
apertures 107 are positioned at the ends of the main flow channel
110a, the sub flow channels 110b through 110f, and the sub flow
channel ef. Note that these well apertures 107 will be
discriminated as well apertures 107A through 107G. The well
apertures 107A through 107G will be collectively referred to as
"well apertures 107".
[0041] The left end (toward the left in FIG. 2) of the main flow
channel 110a is in communication with the well aperture 107A, and
the right end (toward the right in FIG. 2) of the main flow channel
110a is in communication with the well aperture 107G.
[0042] The sub flow channels 110b, 110c, and 110d are flow channels
that branch off from the main flow channel 110a at branching points
210B, 210C, and 210D, respectively. The sub flow channels 110b,
110c, and 110d branch off from the main flow channel 110a toward a
first side thereof (the upper side in FIG. 2), in an inverted T
shape. The sub flow channels 110b, 110c, and 110d are formed along
the main flow channel 110a from the side of the well aperture 107a
with intervals therebetween. Each of the ends of the sub flow
channels 110b, 110c, and 110d are in communication with the well
apertures 107B, 107C, and 107D, respectively.
[0043] The sub flow channel 110ef is a flow channel that branches
off from the main flow channel 110a at a branching point 210EF. The
sub flow channel 110ef branches off from the main flow channel 110a
toward a second side thereof (the lower side in FIG. 2), in a T
shape. The sub flow channel 110ef is formed between the sub flow
channels 110b and 110c. A branching point 210W is provided at the
leading end of the sub flow channel 110ef. Sub flow channels 110e
and 110f are formed to extend parallel to the main flow channel
110a with the branching point 210W therebetween. The ends of the
sub flow channels 110e and 110f are in communication with the well
apertures 107E and 107F, respectively.
[0044] Note that the branching points 210B, 210C, 210D, 210EF, and
210W are collectively referred to as "branching points 210".
[0045] As illustrated in FIG. 2, a measurement target substance
within the sample included in the sample fluid H that flows in the
flow channels 110 is detected by a detecting device having an
optical system.
[0046] The measurement target substance included in the sample
fluid H within the flow channels 110 is processed to emit
fluorescence when excited by external light. The measurement target
substance within the sample fluid H can be detected by detecting
the fluorescence.
[0047] Here, cleansing of the micro-flow channels 110 formed in the
micro-flow channel substrate 102 will be described. Note that the
micro-flow channel cleansing method of the present invention which
is employed to cleanse the micro-flow channels 110 may be applied
to the cleansing of micro-flow channels at a cleansing station of a
clinical analysis apparatus, to be described later.
Comparative Example
[0048] First, a comparative example of a cleansing operation for
the micro-flow channels 110 of the micro-flow channel substrate 102
will be described with reference to FIG. 2 and FIG. 3. In this
comparative example, residual fluids remain on the wall surfaces of
the branching channels when the micro-flow channels 110 are
cleansed, and the quality of cleansing is not high. FIG. 3 is a
magnified plan view of a portion of the micro-flow channels 110
which are formed in the micro-flow channel substrate 102.
[0049] The well apertures 107, which are in communication with the
micro-flow channels 110 that contain the sample fluid H, excluding
the well aperture 107B, that is, the well apertures 107A and 107C
through 107G, are filled with cleansing fluid S.
[0050] Then, the well aperture 107B is employed as a suction
opening. The sample fluid H within the micro-flow channels 110 and
the cleansing fluid S within the well apertures 107A and 107C
through 107G are suctioned through the well aperture 107B.
[0051] As illustrated in FIG. 3, the suction from the well aperture
107B causes the liquids within the micro-flow channels 110 to flow
along fluid trajectories MO1. The wall surfaces of the micro-flow
channels 110 are cleansed by the cleansing fluid that flows along
the fluid trajectories MO1. However, the cleansing fluid S that
approaches branching points from both directions flows in
directions away from the wall surfaces 210Bt, 210EFt, and 210Wt at
branching points 210B, 210EF, and 210W, respectively. Therefore,
almost none of the sample fluid H at the wall surfaces 210Bt,
210EFt, and 210Wt flows away from the wall surfaces, thereby
causing residual fluid to remain thereon.
[0052] That is, the cleansing fluid S that flows into the branching
point 210B from both sides of the wall surface 210Bt flows through
the flow channel 110b toward the well aperture 107B from the
branching point 210B. However, because residual fluid remains on
the wall surface 210Bt, foreign substances on the wall surface
210Bt (contaminants and the like which are attached on the wall
surface 210Bt) are not dissolved or removed therefrom, or only a
small portion of the foreign substances are dissolved or removed.
Accordingly, the foreign substances remain on the wall surface
210Bt.
[0053] Similarly, the cleansing fluid S that flows into the
branching point 210EF from the flow channels 110a and 110ef on
either side of the wall surface 210EFt flows through the flow
channel 110a toward the branching point 210B. However, because
residual fluid remains on the wall surface 210EFt, foreign
substances on the wall surface 210EFt (contaminants and the like
which are attached on the wall surface 210EFt) are not dissolved or
removed therefrom, or only a small portion of the foreign
substances are dissolved or removed. Accordingly, the foreign
substances remain on the wall surface 210EFt.
[0054] Further, the cleansing fluid S that flows from the well
apertures 107E and 107F toward the branching point 210W from the
flow channels 110e and 110f on either side of the wall surface
210Wt flows through the flow channel 110ef toward the branching
point 210EF. However, because residual fluid remains on the wall
surface 210Wt, foreign substances on the wall surface 210Wt
(contaminants and the like which are attached on the wall surface
210Wt) are not dissolved or removed therefrom, or only a small
portion of the foreign substances are dissolved or removed.
Therefore, the foreign substances remain on the wall surface
210Bt.
[0055] Accordingly, it is not possible to remove contaminants and
the like which are attached to the wall surfaces 210Bt, 210EFt, and
210Wt.
First Embodiment
[0056] Hereinafter, a first embodiment of the micro-flow channel
cleansing method of the present invention, which cleanses the micro
channels 110 of the micro-flow channel substrate 102 such that no
residual fluid remains on the wall surfaces of the branching
channels, will be described with reference to FIG. 2, FIG. 4A, and
FIG. 4B. FIG. 4A and FIG. 4B are magnified plan views of a portion
of the micro-flow channels 110 which are formed in the micro-flow
channel substrate 102. FIG. 4A illustrates a state in which
cleansing fluid is suctioned into a sub flow channel, and FIG. 4B
illustrates a state in which cleansing fluid is injected into the
sub flow channel.
[0057] Note that the micro-flow channel cleansing method of the
present invention is the same as the comparative example, which is
not capable of obtaining high cleansing quality, up to a point.
[0058] In a manner similar to that of the comparative example, the
well apertures 107, which are in communication with the micro-flow
channels 110 that contain the sample fluid H, excluding the well
aperture 107B, that is, the well apertures 107A and 107C through
107G, are filled with cleansing fluid S.
[0059] Then, the well aperture 107B is employed as a suction
opening. The sample fluid H within the micro-flow channels 110 and
the cleansing fluid S within the well apertures 107A and 107C
through 107G are suctioned through the well aperture 107B. That is,
the sample fluid H and the cleansing fluid S are suctioned through
a single flow channel 110b, which is in communication with the
branching points 210B, 210W, etc. within the micro-flow channels
110.
[0060] In a manner similar to that of the comparative example (as
illustrated in FIG. 4A), the suction from the well aperture 107B
causes the liquids within the micro-flow channels 110 to flow along
fluid trajectories M11. The fluid trajectories Mil are the same as
the fluid trajectories M01 of the comparative example. Therefore,
almost none of the sample fluid H at the wall surfaces 210Bt,
210EFt, and 210Wt flows away from the wall surfaces, thereby
causing residual fluid to remain thereon. Accordingly, it is not
possible to remove contaminants which are attached to the wall
surfaces 210Bt, 210EF1, and 210W1 with the steps of the method up
to this point.
[0061] Next, as illustrated in FIG. 4B, the well aperture 107B is
employed as an injection opening for the cleansing fluid S, and the
cleansing fluid S is injected through the well aperture 107B into
the flow channel 110b and the other micro-flow channels via the
branching point 210B. That is, the cleansing fluid S is injected
into the flow channel 110b, which is in communication with the
branching points 210B, 210W, etc. within the micro-flow
channels.
[0062] The injection of the cleansing fluid S causes the cleansing
fluid S to flow through the micro-flow channels along fluid
trajectories M12. That is, the direction of flow of the fluid that
passes through the micro-flow channel is reversed from the case in
which the cleansing fluid S is suctioned. Thereby, the wall
surfaces 210Bt, 210EFt, and 210Wt, at which the sample fluid H had
remained, become in a state in which they are showered with the
cleansing fluid S (a state in which the cleansing fluid S flows
thereon). Accordingly, cleansing effects, such as the foreign
substances attached to the wall surfaces (contaminants and the like
which are attached to the wall surfaces) being dissolved or
physically removed, are obtained, and the foreign substances can be
removed from the wall surfaces.
[0063] Therefore, the wall surfaces 210Bt, 210EFt, and 210Wt can be
cleansed in a manner similar to that in which other wall surfaces
are cleansed. That is, the foreign substances can be removed from
the wall surfaces 210Bt, 210EFt, and 210Wt.
[0064] The first embodiment changes the direction in which the
cleansing fluid S is caused to flow through the branching points
210B, 210EF, and 210W, by performing injection of the cleansing
fluid S into a specific flow channel 110b, which is in
communication with the branching points 210B, 210EF, and 210W
within the micro-flow channels 110, and suction of the cleansing
fluid S from the specific flow channel 110b. The quality of
cleansing of the wall surfaces of the branching points can be
improved, by changing the direction in which the cleansing fluid S
is caused to flow with respect to the branching points.
[0065] Note that the micro-flow channels are not limited to being
cleansed by performing suction and injection through a single flow
channel. Suction may be performed simultaneously through two or
more specific flow channels, then injection may be performed
simultaneously through the two or more specific flow channels, to
cleanse the micro-flow channels 110.
Second Embodiment
[0066] Next, a second embodiment of the micro-flow channel
cleansing method of the present invention will be described with
reference to FIG. 5A and FIG. 5B. FIG. 5A and FIG. 5B are magnified
plan views of a portion of the micro-flow channels 110 which are
formed in the micro-flow channel substrate 102. FIG. 5A illustrates
a state in which cleansing fluid is suctioned through the well
aperture 107B, and FIG. 5B illustrates a state in which cleansing
fluid is suctioned through the well aperture 107F.
[0067] In a manner similar to that of the first embodiment, the
well apertures 107, which are in communication with the micro-flow
channels 110 that contain the sample fluid H, excluding the well
aperture 107B, that is, the well apertures 107A and 107C through
107G, are filled with cleansing fluid S. Then, the well aperture
107B is employed as a suction opening. The sample fluid H within
the micro-flow channels 110 and the cleansing fluid S within the
well apertures 107A and 107C through 107G are suctioned through the
well aperture 107B. The suction from the well aperture 107B causes
the liquids within the micro-flow channels 110 to flow along fluid
trajectories M21. The fluid trajectories M21 are the same as the
fluid trajectories M01 of the comparative example and the fluid
trajectories M11 of the first embodiment. Therefore, almost none of
the sample fluid H at the wall surfaces 210Bt, 210EFt, and 210Wt
flows away from the wall surfaces, thereby causing residual fluid
to remain thereon. Accordingly, it is not possible to remove
contaminants which are attached to the wall surfaces 210Bt, 210EF1,
and 210W1 with the steps of the method up to this point.
[0068] Next, as illustrated in FIG. 5B, the suction opening is
changed to the well aperture 107F. The well apertures 107 excluding
the well aperture 107F, that is, the well apertures 107A through
107E and 107G, are filled with cleansing fluid S, and the cleansing
fluid S is suctioned through the well aperture 107F.
[0069] The suction of the cleansing fluid S through the well
aperture 107F causes the cleansing fluid S to flow through the
micro-flow channels along fluid trajectories M22. Thereby, the wall
surfaces 210Bt, 210EFt, and 210Wt, at which the sample fluid H had
remained, become in a state in which the cleansing fluid S flows
thereon. Accordingly, cleansing effects, such as the foreign
substances attached to the wall surfaces (contaminants and the like
which are attached to the wall surfaces) being dissolved or
physically removed (pushed away by the flow), are obtained, and the
foreign substances can be removed from the wall surfaces.
[0070] Therefore, the wall surfaces 210Bt, 210EFt, and 210Wt can be
cleansed in a manner similar to that in which other wall surfaces
are cleansed. That is, the foreign substances can be removed from
the wall surfaces 210Bt, 210EFt, and 210Wt.
[0071] The second embodiment changes the direction in which the
cleansing fluid S is caused to flow through the branching points
210B, 210EF, and 210W, by performing injection or suction of the
cleansing fluid S through each of two specific flow channels 110b
and 110f, which are in communication with the branching points
210B, 210EF, and 210W within the micro-flow channels 110. The
quality of cleansing of the wall surfaces of the branching points
can be improved, by changing the direction in which the cleansing
fluid S is caused to flow with respect to the branching points.
[0072] The micro-flow channels are not limited to being cleansed by
performing suction of cleansing fluid through a first flow channel
of two different flow channels that have the branching channels
therebetween and communicate therewith, then performing suction of
the cleansing fluid through a second flow channel, to change the
direction in which the cleansing fluid flows with respect to the
branching channels. Alternatively, the cleansing fluid may be
suctioned through the first flow channel of the two different flow
channels that have the branching channels therebetween and
communicate therewith, and then the cleansing fluid may be injected
from the second flow channel, in order to change the direction in
which the cleansing fluid flows with respect to the branching
channels during cleansing thereof.
[0073] As another alternative, the cleansing fluid may be injected
into the first flow channel of the two different flow channels that
have the branching channels therebetween and communicate therewith,
and then the cleansing fluid may be suctioned through the second
flow channel, in order to change the direction in which the
cleansing fluid flows with respect to the branching channels during
cleansing thereof.
[0074] As a further alternative, the cleansing fluid may be
injected into the first flow channel of the two different flow
channels that have the branching channels therebetween and
communicate therewith, and then the cleansing fluid may be injected
into the second flow channel, in order to change the direction in
which the cleansing fluid flows with respect to the branching
channels during cleansing thereof.
[0075] Note that the micro-flow channels are not limited to being
cleansed by performing injection into a single flow channel.
Injection may be performed into two or more flow channels. In
addition, the micro-flow channels are not limited to being cleansed
by performing suction from a single flow channel. Suction may be
performed from two or more flow channels.
[0076] In the embodiments described above, the branching points are
those that branch in T shapes. However, the branching points are
not limited to those that branch in T shapes. The micro-flow
channel cleansing method of the present invention may be applied to
branching points that branch in any shape, such as a Y shape.
<Clinical Analysis Apparatus>
[0077] Hereinafter, an example of a clinical analysis apparatus
that utilizes the micro-flow channel cleansing method of the
present invention will be described. That is, a case in which the
micro-flow channels are formed in a microchip to be utilized in the
clinical analysis apparatus, and reagents and samples are
introduced thereinto, will be described with reference to FIG. 6
through FIG. 11. FIG. 6 is a perspective view that illustrates the
outer appearance of the clinical analysis apparatus.
[0078] As illustrated in FIG. 6, the apparatus 1 is constituted by:
a casing 2; a stocking section 8, provided in the casing 2; a
measuring section 10 provided in the vicinity of the stocking
section 8; and a dispensing mechanism 12 that moves reciprocally
between the stocking section 8 and the measuring section 10. Covers
4 and 5, which are openable and closable with respect to the casing
2, are provided to cover the measuring section 10 and the stocking
section 8, respectively. The covers 4 and 5 are configured such
that they cannot be opened during detection of samples and
cleansing operations. The stocking section 8 includes a circular
reagent bay 8a and a sample holding section 8b. The sample holding
section 8b includes an annular member 14 that surrounds the
periphery of the reagent bay 8a. Note that the reagent bay 8a and
the sample holding section 8b are rotatable. However, drive sources
such as motors for rotating the reagent bay 8a and the sample
holding section 8b have been omitted from FIG. 3. A plurality of
cutouts 14a for holding sample containers 3b are formed in the
annular member 14 at predetermined intervals. Note that the
interior of the stocking section 8 is cooled by a cooling device
(not shown).
[0079] A display panel 16 constituted by an LCD or the like is
provided on the upper surface 2a of the casing 2. The display panel
16 displays the names of tests, and enables selection of the
contents of measurement (items to be measured) for each sample. A
printer 18 for printing out detection results obtained by a
detecting station 46 is provided in the vicinity of the display
panel 16. A parallelepiped cleansing water container 20 and a
parallelepiped waste liquid container 22 are mounted on the
exterior of the casing 2 in the vicinity of the stocking section 8.
The cleansing water container 20 contains water for cleansing the
microchips 100 and the like. The waste liquid container 22 contains
all waste liquids.
[0080] The dispensing mechanism 12 includes: a moving body 12a; and
a probe 12b, which is attached to the moving body 12a.
[0081] Next, the measuring section 10 will be described with
combined reference to FIG. 6 and FIGS. 7 through 11. FIG. 7 is a
magnified perspective view of the measuring section 10, in which
microchips 100 are provided. FIG. 8 is a schematic plan view that
illustrates the stocking section 8 and the measuring section 10 as
the main parts of the apparatus 1.
[0082] The measuring 10 is equipped with: a drive source (not
shown) that functions as a conveyance mechanism for conveying the
microchips 100; and a rotating table 40 which is driven to rotate
counterclockwise by the drive source. The rotating direction of the
rotating 40 is unidirectional in the counterclockwise direction,
and the drive source is not configured to enable clockwise
rotation.
[0083] Eight bases are provided on the rotating table 40 at a
predetermined pitch. A microchip 100 is to be placed on each of the
bases. When the rotating table 40 is viewed from above as
illustrated in FIG. 7, eight recesses 42a are formed at the
predetermined pitch (angular pitch), and the bases are housed
within the recesses 42a. Accordingly, when the microchips 100 are
placed within the recesses 42a, the microchips 100 are placed on
the bases which are provided corresponding to the recesses 42a.
[0084] Eight stations 42, 44, 46, 48, 50, 52, 54, and 56 are
provided in the casing 2 at the same predetermined pitch (angular
pitch). Accordingly, a microchip 100 is to be placed at positions
corresponding to each of the stations 42 through 56.
[0085] The first station, at which the measurement operation is
initiated, is a dispensing station 42, at which samples and the
like are dispensed into the microchips 100 by the probe 12b of the
dispensing mechanism 12. That is, the dispensing station 42 is
where the first step in the measurement operation is performed.
[0086] The remaining stations, that is, an introducing station 44;
a detecting station 46; cleansing stations 47; and a microchip
attaching/removing station 56, for attaching and removing the
microchips 100, are provided on the rotating table 40 in this order
in the counterclockwise direction. Note that in the present
embodiment, the cleansing stations 47 include four stations, that
is, a chemical cleansing station 48, water cleansing stations 50
and 52, and a residual liquid suctioning station 54. The four
cleansing stations 48, 50, 52, and 54 perform a chemical cleansing
step, a first water cleansing step, a second water cleansing step,
and a residual liquid suctioning step, respectively. Note that the
element denoted by reference numeral 13 in FIG. 8 (User Interface
Section) is a so-called operating panel.
[0087] Cover members 44b, 46b, and 52b are mounted on the casing 2
such that they are capable of approaching and separating from the
rotating table 40, to perform opening and closing operations.
Accordingly, only the rotating table 40 rotates, and the cover
members 44b, 46b, and 52b do not move within a plane parallel to
the rotating table 40.
[0088] Next, each of the stations 42, 44, 46, 47 (48, 50, 52, 54),
and 56 will be described further, with reference to FIG. 7 and FIG.
8.
[0089] The eight stations are provided about the circumference of
the rotating table 40 such that they are equidistant from each
other. Therefore, the amount of time spent performing operations at
each of the eight stations 42 through 56 is the same, for example,
200 seconds. That is, after 200 seconds pass, the rotating table 40
rotates to the next step. Accordingly, one cycle is completed after
a single rotation of 200.times.8=1600 seconds, and measurement
operations for a first microchip 100 are completed. Thereafter, the
measurement operations for the remaining microchips 100 are
sequentially completed after 200 second intervals.
[0090] When a microchip 100 is placed at a position corresponding
to the dispensing station 42, the moving body 12a of the dispensing
mechanism 12 moves above the microchip 100, and samples and the
like are dripped into a predetermined well 106 by the probe 12b.
This operation is repeated for all of the wells 106 into which
reagents or samples are to be dripped (first step).
[0091] A cover member 44b is provided at the introducing station 44
so as to be openable and closable. Tubes 44c for communicating with
predetermined wells 106 of the microchip 100 when the microchip 100
is placed at the introducing station 44 are mounted on the cover
member 44b. Pressurized gas is supplied into the wells C and D
illustrated in FIG. 2 via the tubes 44c (second step).
[0092] A cover member 46b is also mounted on the detecting station
46. Electrodes (not shown) for applying voltages used in
electrophoresis are provided on the underside of the cover member
46b. The electrodes are positioned to correspond to the wells A, F,
and G, through which the voltages are applied.
[0093] A light measuring section 58 of the detecting station 46 has
the aforementioned detecting device 6 (refer to FIG. 2)
incorporated therein. Electrophoretic voltages are applied to the
electrodes at the detecting station 46, to cause electrophoresis of
the sample (third step). During electrophoresis, the sample is
maintained in a low temperature state, for example, in a state in
which the temperature of the sample fluid is 10.degree. C.,
depending on the sample.
[0094] The wells 106 to which voltages are applied to are switched
(fourth step). Electrophoreses is continued in a state in which the
temperature of the sample fluid is maintained at 10.degree. C., and
measurement of the measurement target substance is performed (fifth
step).
[0095] Next, the cleansing stations 47 that employ the micro-flow
channel cleansing method of the present invention will be described
in detail.
[0096] The cleansing stations 47 include the four stations 48, 50,
52, and 54, each of which performs a single cleansing step. The
chemical cleansing station 48 employs a chemical (cleansing agent)
such as NaOH (sodium hydroxide) to cleanse the flow channels 110 of
used microchips 100. The chemical cleansing station 48 is
configured to cleanse wells 106 contaminated by samples, by
discharging the chemical into the wells 106 and then suctioning it
out. At this time, the chemical is suctioned from the flow channels
110 at a negative pressure of for example, 300 g/cm.sup.2.
[0097] FIG. 9 is a magnified perspective view that illustrates the
main parts of the chemical cleansing station 48. Cleansing of the
micro-flow channels is performed by the micro-flow channel
cleansing method of the present invention at the chemical cleansing
station.
[0098] Probes 48p and 48q are configured to inject and suction
chemicals into and from each of the flow channels 110 within the
flow channel substrate 102 of the microchip 100. The probes 48p and
48q are capable of moving in the directions indicated by arrow 60.
This movement is performed employing a motor 48c illustrated in
FIG. 4, and a threaded shaft 48d, which is driven by the motor 48c
(refer to FIG. 7). That is, a member 48e that supports the
microchip 100 is engaged with the threaded shaft 48d, and the
microchip 100 is moved reciprocally in the radial direction of the
rotating table 40 by rotation of the threaded shaft 48d.
[0099] Note that only the tips of the probes 48p and 48q are
illustrated in FIG. 9. However, the probes 48p and 48q extend as
illustrated by the broken lines, or have tubes attached thereto. A
chemical (cleansing agent) container 15 and a probe cleansing tank
17 are also provided in the chemical cleansing station 48. The
cleansing agent is contained in the chemical container 15. The
cleansing agent is supplied to the wells 106 by the probes 48p and
48q. During the chemical cleansing operation, the tips of the
probes 48p and 48q are inserted into the wells 106, and therefore
the tips of the probes 48p and 48q are cleansed within the probe
cleansing tank 17 after each insertion. Openings 65a that
communicate with a syringe pump (not shown) are formed in a sealing
plate 65 at positions that correspond to the wells 106. Pressure
supplied by the syringe pump is utilized to expel the chemical from
the wells 106 and the micro-flow channels 110.
[0100] The chemical is injected into specific wells 106, and
suctioned out from other wells 106 at the aforementioned negative
pressure of 300 g/cm.sup.2. The manner of cleansing will be
described with combined reference to FIG. 10.
[0101] FIG. 10 is a magnified sectional view that illustrates the
concept of cleansing of a well 106 and the application of negative
pressure on another well 106. FIG. 10 illustrates a state in which
the probe 48p is inserted into a well 106, while injecting and
suctioning a chemical 62 such that it does not overflow from the
well 106.
[0102] FIG. 10 also illustrates a state in which another well 106
is sealed by sealing members 64 and the sealing plate 65, while
negative pressure is applied to perform suction.
[0103] In this manner, the samples and chemical 62 are injected
into and suctioned from the wells 106 and the flow channels 110
while the probes 48p and 48q move. Thereby, the flow channels 110
are sufficiently cleansed by the micro-flow channel cleansing
method of the present invention. Accordingly, the degree of
cleansing is high. Note that the portion denoted by reference
number 102 in FIG. 7 corresponds to the micro-flow channel
substrate 102.
[0104] After the chemical cleansing step, the water cleansing
station 50 performs injection and suction of water to all of the
wells 106 in the same manner as described above.
[0105] The water cleansing station 50 also executes cleansing of
the micro-flow channels using the micro-flow channel cleansing
method of the present invention. The difference is that the
cleansing fluid employed at the water cleansing station 50 is
water.
[0106] Further, the water cleansing station 52 expels the chemical
from the flow channels 110 with a water pressure of, for example,
10 kg/cm.sup.2. At this time, the well 106 through which the water
and the chemical are expelled is open to the atmosphere, and the
expelled waste liquid is contained in the waste liquid container
22.
[0107] The water cleansing station 52 may also execute cleansing of
the micro-flow channels using the micro-flow channel cleansing
method of the present invention. The cleansing fluid employed at
the water cleansing station 52 is also water.
[0108] Next, residual fluid is suctioned from the wells 106 at the
residual fluid suctioning station 54. This operation is performed
by a probe 54p (refer to FIG. 7), which is connected to a negative
pressure source, being inserted into the wells 106'.
[0109] Next, the cleansed microchips 100 are conveyed to the
microchip attaching/removing station 56. If a microchip 100 has
been used a predetermined number of times, which is considered to
be its usable lifetime, for example, 10 to 200 times, the microchip
attaching/removing station 56 removes the microchip 100 and mounts
a new microchip 100 on the rotating table 40. The microchip
attaching/removing station 56 only functions when exchanging
microchips 100, and does not operate during normal measurement.
[0110] FIG. 11 illustrates magnified perspective views of the
manner in which the microchips 100 are exchanged at the microchip
attaching/removing station 56. FIG. 11A illustrates a state in
which a microchip is standing by at the attaching/removing station,
and FIG. 11B illustrates a state in which a microchip is being
discharged from the attaching/removing station.
[0111] An opening 56ccorresponding to a recess 56a of the rotating
table 40 is provided, for example, in the casing 2, at the
microchip attaching/removing station 56. The opening 56cmay be open
at all times, or an appropriate lid (not shown) may be provided to
open and close the opening 56c.
[0112] A microchip 100 at the end of its useful lifetime can be
accessed through the opening 56cand removed, and a new microchip
100 may be loaded through the opening 56c. In order to judge
whether a microchip 100 has reached the end of its useful lifetime,
a wireless tag 101 (recording portion) may be provided on the
microchip 100. The number of times that the microchip 100 has been
used may be automatically be recorded in the wireless tag 101, and
when a predetermined number is reached, a message prompting
exchange of the microchip 100 may be displayed on the display panel
16. Alternatively, an operator may be notified of the need to
exchange microchips 100 by an appropriate audio signal. The
counting of the number of uses and recording of the number of uses
into the wireless tag 101 may be managed by a control section 11
(refer to FIG. 8), provided on the rear side of the apparatus 1,
for example. Note that the wireless tag 101 may be provided at a
desired position on the microchip 100 by fitting, embedding, or any
other means.
[0113] Note that in the present embodiment, the microchips 100 are
rotated through the stations. Alternatively, the stations may be
rotated to perform their respective processes on the microchips
100. In addition, the cleansing stations 47 include the plurality
of cleansing stations that perform different cleansing steps.
Alternatively, the plurality of cleansing steps may be performed by
a single cleansing station. Further, in the above embodiment, the
reagents and samples are introduced into the wells by being
pressurized. Alternatively, the reagents and samples may be
introduced into the wells by suctioning from an opposing well. The
pressurization and suction may be performed independently, or
simultaneously.
* * * * *